Related Experiment Video
Updated: Jun 19, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Discrepancies between antiangiogenic and antitumor effects of recombinant human endostatin
1Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, People's Republic of China.
Abstract:
It has been widely accepted that antiangiogenesis therapy could deprive tumor cells of nutrients and oxygen and suppress tumor growth. However, in the present study, Lewis lung carcinomas and A549 adenocarcinomas established in male C57BL/6 and BALB/c nude mice, respectively, were treated with recombinant human endostatin (rh-endostatin). Earlier studies document discrepancies in the antiangiogenic and antitumor outcomes of rh-endostatin treatment, at doses equivalent to clinical usage. Although there was no significant regression of tumor growth, tumor vasculature was widely disrupted within the first few days of treatment with rh-endostatin, as indicated by reduced blood perfusion (visualized by dynamic-contrast-enhanced magnetic resonance imaging) and reduced microvascular density. Interestingly, when rh-endostatin treatment was discontinued, there was an elevation in the diffusion of oxygen and tetramethylrhodamine isothiocyanate-dextran in both tumor classes, which was detected by hypoxyprobe (pimonidazole) and fluorescence microscopy. We conclude that the paradoxic outcomes in the antiangiogenic and antitumor properties of rh-endostatin might derive from the tumors' tolerance to antiangiogenesis inhibitors. Additionally, rh-endostatin might have the ability to transiently normalize tumor vasculature.
Insights
Recombinant human endostatin (rh-endostatin) disrupted tumor vasculature but did not significantly inhibit tumor growth. Tumors showed increased oxygen and dextran diffusion after rh-endostatin treatment cessation, suggesting transient normalization.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Antiangiogenesis therapy aims to starve tumors by inhibiting blood vessel formation.
- Recombinant human endostatin (rh-endostatin) is a clinically used antiangiogenesis agent.
- Previous studies show conflicting results regarding rh-endostatin's efficacy.
Purpose of the Study:
- To investigate the antiangiogenic and antitumor effects of rh-endostatin in mouse tumor models.
- To explore the impact of rh-endostatin on tumor vasculature and nutrient/oxygen diffusion.
- To understand the paradoxical outcomes observed with rh-endostatin treatment.
Main Methods:
- Lewis lung carcinomas and A549 adenocarcinomas were established in mice.
- Tumor-bearing mice were treated with rh-endostatin at clinical doses.
- Dynamic-contrast-enhanced MRI assessed tumor blood perfusion.
- Microvascular density, oxygen diffusion (hypoxyprobe), and dextran diffusion were measured.
Main Results:
- Rh-endostatin treatment disrupted tumor vasculature, reducing blood perfusion and microvascular density.
- No significant tumor growth regression was observed.
- Discontinuation of rh-endostatin led to increased oxygen and dextran diffusion in tumors.
- These effects were observed in both Lewis lung carcinomas and A549 adenocarcinomas.
Conclusions:
- Paradoxical outcomes of rh-endostatin may stem from tumor tolerance to antiangiogenesis inhibitors.
- Rh-endostatin may transiently normalize tumor vasculature, potentially impacting drug delivery and hypoxia.
- Further research is needed to optimize antiangiogenesis strategies and overcome resistance mechanisms.
More Related Videos
08:46Strategic Endothelial Cell Tube Formation Assay: Comparing Extracellular Matrix and Growth Factor Reduced Extracellular Matrix
Published on: August 14, 2016
14:20Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014